The goal of this proposal is to bring a Thermo Fisher Scientific Orbitrap hybrid FT mass spectrometer with ETD and nano-LC to the Proteomics Core at Wayne State University. This instrument, has unique capabilities for peptide sequencing and protein identification due to the high resolution and 1-2 ppm mass accuracy. The capabilities of the Orbitrap Velos make it an exceptional instrument fo proteomic profiling, spectral counting and isotopic based quantitation. The availability of the Orbitrap Velos and trained operators in the Proteomics Core will be a major asset to research programs of NIH-funded investigators at WSU and in the SE Michigan region. The instrument will address two critical needs that are currently not adequately met. The first of these is for unambiguous protein identification based on accurate mass of peptide precursor and daughter ions. The second is localization of post translational modifications (PTM) in large protein fragments that can maintain multiple PTMs in a single peptide. The only currently available MS/MS instruments at Wayne State University or in the metropolitan Detroit area that can be used for proteomic analysis is the LTQ-XL with ETD that is operated by the same Proteomics Core seeking to add the Orbitrap. The Proteomics Facility Core is the only source for proteomic services at Wayne State. The University is strongly committed to this proposal as evidenced by the following support: 1) A commitment to fund the general operations of the Core at $125,000 per year. 2) $214,000 in matching funds to purchase the instrument. 3) $75,000 from the SOM to defray some of the cost for a long term service contract to ensure continual operation of the Orbitrap. The Orbitrap with ETD is a state-of-the-art system with unparalleled ability to determine the accurate mass of peptides and protein fragments and to localize post-translational modifications in proteins. At WSU, this instrument will allow more productive use of instrumentation already in place for proteomic fractionation and will provide efficient access to modern proteomic analysis for NIH-funded investigators. PUBLIC HEALTH RELEVANCE: Understanding disease processes and validating medical therapies requires us to discover and measure the proteins and the changes in proteins in our cells. The Orbitrap Velos with ETD mass spectrometer system accurately identifies proteins and protein modifications in intact proteins, large protein fragments and peptides. Adding the Orbitrap to the WSU proteomics Core will provide essential analytical services to dozens of NIH funded researchers.